Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients (LIVERAL)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01022476
First received: November 26, 2009
Last updated: July 17, 2013
Last verified: July 2013

November 26, 2009
July 17, 2013
May 2010
May 2013   (final data collection date for primary outcome measure)
Pharmacokinetic parameters of raltegravir in patients with severe liver dysfunction and after a liver transplantation when combined to immunosuppressive therapy. Pharmacokinetic parameters of immunosuppressive drugs with or without raltegravir [ Time Frame: at month 1 for period 1 and day 7-month 1 for period 2 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01022476 on ClinicalTrials.gov Archive Site
  • To assess the maintenance of the virological efficacy on HIV of raltegravir combined with two fully active molecules among NRTI (or NRTI + enfuvirtide). Follow-up over a 3-months period before and after transplantation [ Time Frame: from day 0 to month 3 for period 1 and period 2 ] [ Designated as safety issue: Yes ]
  • To assess the safety of raltegravir before transplantation in patients with impaired liver function, and after transplantation in combination with immunosuppressive treatment [ Time Frame: from day 0 to month 3 for period 1 and period 2 ] [ Designated as safety issue: Yes ]
  • To describe the clinical outcome of patients (such as the onset of opportunistic infections, relapse of HCV infection, morphological and metabolic disorders outcomes) [ Time Frame: from day 0 to month 3 for period 1 and period 2 ] [ Designated as safety issue: No ]
  • To describe the changes in liver function (evaluation of liver function during treatment) before and after liver transplantation [ Time Frame: from day 0 to month 3 for period 1 and period 2 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients
A Pilot Study of Pharmacokinetics, Tolerance and Efficacy of Raltegravir Combined to Two Fully Active Molecules Among Nucleosi(ti)de Analogs and Enfuvirtide Before and After Liver Transplant in HIV Infected Patients With End Stage Liver Disease (ANRS 148 LIVERAL)

This phase I/II, multi-center study is designed to determine the pharmacokinetic profile of Raltegravir in patients with end stage liver disease and to assess drug-drug interaction when Raltegravir is combined with immunosuppressive therapy in liver transplant recipients.

HIV infected patients with stable plasma HIV-RNA below 50 copies per mL and severe liver dysfunction will be switched from their antiretroviral regimen to a combination of raltegravir (one 400 mg pill twice daily) and two fully active molecules among nucleosi(ti)de analogs and enfuvirtide for a first period of at least 3 months and a second period of at least 3 months after liver transplantation, if need be, when a steady state of the anticalcineurin will be reached. Pharmacokinetic parameters of raltegravir will be calculated during severe liver dysfunction period and after liver transplantation. Pharmacokinetic parameters of cyclosporine (or tacrolimus if contra indication to cyclosporine) will be compared when administrated alone or combined with raltegravir. Patients will be followed up according to standard of care. This study will be divided in two distinct periods (1 and 2) lasting 3 months each. Period 1 will start from the inclusion in the study and will generally include the switch to raltegravir. Period 2 will start from liver transplantation.

Interventional
Phase 1
Phase 2
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • Liver Failure
  • Evidence of Liver Transplantation
Drug: Raltegravir potassium
one pill of raltegravir 400 mg twice a day
Other Name: ISENTRESS
Experimental: Raltegravir potassium
raltegravir 400 mg twice a day
Intervention: Drug: Raltegravir potassium
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
May 2013
May 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age ≥ 18
  • Documented HIV-1 infection, hepatitis B or C co-infection is allowed
  • Plasma viral load at screening visit below 50 copies per mL for at least 6 months
  • Patient with severe liver failure (Meld Score ≥ 15 and/or refractory ascites and/or haemorrhage of digestive tract and/or hepatic encephalopathy) for taking part into period 1
  • Patient eligible for the liver transplant waiting list or immediate post transplantation for taking part into period 2
  • Abstinence from alcohol intake for at least 6 months (WHO norm)
  • Withdrawal from intravenous drug use for at least 6 months (methadone substitution is permitted)
  • No ongoing class C opportunistic infection (1993 CDC classification)
  • Patient whose clinical and immunovirological condition allows triple therapy with raltegravir + 2 NRTI or raltegravir + NRTI + enfuvirtide
  • Patient whose HIV population, according to cumulative genotypes carried out on viral RNA together with treatment history (if available and interpreted as per the ANRS-AC11 algorithm version no.19) does not present a profile of mutations associated with resistance to raltegravir and is sensitive to at least two fully active* agents selected among nucleoside/nucleotide reverse transcriptase analogs NRTI (abacavir, lamivudine, emtricitabine, tenofovir) or enfuvirtide

    *An ARV agent is considered to be fully active if the cumulative genotypes do not show any mutation associated with resistance or any mutation associated with "possible resistance"

  • Patient not having experienced viral escape during treatment combining 3TC, FTC or raltegravir
  • Patient registered with or covered by a social security scheme
  • For women of child-bearing potential, use of a barrier contraceptive method during sexual intercourse and negative pregnancy test (plasma ß-HCG ) at screening visit
  • Informed consent form signed at screening visit at the latest

Exclusion Criteria:

  • More than two virological failures during antiretroviral treatment
  • Currently receiving treatment with an agent in development (apart from an authorization for temporary use)
  • Plasma viral load at screening visit ≥ 50 copies per mL during at least the last 6 months
  • Pregnant women, or women liable to become pregnant, breast-feeding women, no contraception, or refusal to use contraception
  • All conditions (including but not limited to alcohol intake and drug use) liable to compromise, in the investigator's opinion, the safety of treatment and/or the patient's compliance with the protocol
  • Patient not having any effective options for NRTI +/- enfuvirtide (defined in the inclusion criteria)
  • Ongoing treatment with interferon-alpha or ribavirin for hepatitis C
  • Concomitant medication including one or more agents liable to induce UGT1A1 and reduce raltegravir concentrations:

    • anti-infective agents: rifampicin/rifampin
    • psychotropic/antiepileptic agents: phenytoin, phenobarbital, carbamazepine
    • steroidal anti-inflammatory drug: dexamethasone
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01022476
2009-014616-36, ANRS 148 LIVERAL
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Merck Sharp & Dohme Corp.
Principal Investigator: Elina TEICHER, MD Hôpital de Bicêtre - LE KREMLIN-BICETRE - FRANCE
Study Chair: Jean-Pierre ABOULKER, MD INSERM SC10 VILLEJUIF FRANCE
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP